Structure Tools and Visualization

Transcription

1 Structure Tools and Visualization Gary Van Domselaar University of Alberta Slides Adapted from Michel Dumontier, Blueprint Initiative 1

2 Visualization & Communication Visualization tools allow us to see 3D structure data communicate features about 3-D structures to colleagues illustrate biological processes (catalytic/binding) educate laypersons about structural biology Go beyond Rasmol & communicate other structural features surface shape show the surface, transparent over a backbone hydrophobicity / charge show the binding surfaces or charge complementarity mutations making a simple model (e.g. 1 amino acid change) 2

3 In this lecture we introduce Rasmol and CHIME Good introductory packages for biomolecule visualization Cn3D for Structure Annotation Good all around viewer that uses OpenGL graphics Good annotation engine for exchanging information about 3D structure Swiss PDB Viewer (Deep View) Make molecular surfaces Align multiple proteins Apply scoring functions Simple, fast modeling including site-directed mutagenesis Complex modeling including loop rebuilding PyMOL Python based, can be used for scripting 3

4 Rasmol & CHIME Developed by Roger Sayle Open source, binaries available Widely used, simple to use (menus) for simple operations Complex operations require command-line interface 4

5 Rasmol Developed by Roger Sayle Open source, binaries available Widely used, simple to use (menus) for simple operations Complex operations require command-line interface 5

6 Getting Rasmol Structure Files Uses PDB files:

7 Working With the PDB File select cys115.cb select lys116 7

8 Hen egg-white lysozyme and tri-n-acetylchitotriose 8

9 Rasmol Help Quick Reference Card: Rasmol Manual Tutorials: Gallery: 9

10 CHIME CHIME: Chemical mime A free molecular viewer web browser plugin based on Rasmol Developed by MDL Information Systems Inc: Improves on Rasmol: More commands Hypertext button-controlled scripting Animations 10

11 CHIME What you need to run CHIME: Netscape / Mozilla / Internet Explorer Windows or Macintosh A web page designed to use CHIME A PDB file 11

12 CHIME and Protein Explorer Protein Explorer: A website that works with CHIME to help you visualize your structures 12

13 Cn3D Developed by the NCBI Open source, binaries available Fast OpenGL Graphics Annotation Engine Lets you mark up a protein at the residue level Can fetch a structure over the Internet Can display protein movies NMR ensembles Protein folding trajectories 13

14 Getting Cn3D Structure Files Uses MMDB files Entrez ( tightly coupled with MMDB structure database Retrieve using MMDB identifier PDB identifer Conserved Domain Database BLAST search PubMed query Text search 14

15 Hen egg-white lysozyme and tri-n-acetylchitotriose 15

16 ASN.1 Structure File (ascii) MMDB-ID PDB ID History Publications Chemical Graph - Molecule Graph - taxonomy - residue sequence - inter residue bonds - heterogens - solvent - Inter-molecule bonds - Annotation - Camera Settings 16

17 Global Style Settings 17

18 Create New Annotation Disulfide Cysteines Select Residues Menu>Style>Annotate Create New Annotation Give Name and Edit Style 18

19 Edit Style Options 19

20 Selective Annotation of Cysteine Disulfide Bridges 20

21 Annotation Menu Turn On/Off Show/Hide selected annotation Move Up/Down Change priority Show Show annotation and affected residues Edit Edit an existing annotation Move Move the annotation to selected residues Delete Delete the Annotation 21

22 Shortcuts Rendering: SpaceFill Coloring: Rainbow Rendering: Ball and Stick Coloring: Hydrophobicity 22

23 Another Salient Feature Show/Hide>Select by distance 23

24 Imports Import sequences BLAST alignments Import structures Structural Superposition 24

25 BLAST Create alignments between sequences In this case, an alignment between the structure sequence and the natural sequence reveals missing N and C termini residues and a loop region, not resolved in structure. 25

26 Conserved Domain Alignments 26

27 Folding Simulations 27

28 NMR Solution Structures 28

29 Finishing Your Work Save Annotations Camera Settings Export PNG image 29

30 Other Cn3D Resources Application Help Online Help 30

31 Swiss PDV Viewer at a Glance PDB structure viewer with structure utilities Superimposition to compare proteins and their components such as active/binding sites Measure angles, distances between atoms Manual or automated (Swiss-Model) homology modeling including loop modeling Threading (Fold recognition) Mutations and Energy minimization Electron density map reading and model building (crystallography data) Interface to POV-Ray rendering software 31

32 Main Interface Tons of menu options reasonably well categorized Button bar for image manipulation (center, zoom, move, rotate) and some structure measurement and mutation tools Layers window to select from multiple layers 32

33 Control Panel Select Individual Residues (one or more) All Residues Chains Secondary Structure Show Backbone Side chains Labels Molecular surface (VDW) Ribbon Cartoons (Helices/Strands) Colors (specify backbone +/- sidechain, labels, etc) 33

34 Alignment and Ramachandran Plot Alignment Window shows alignment of sequences to one another (structural superposition, threading / homology modelling) Ramachandran plot showing Phi-Psi angles of selected residues. Can move individual residues to new Phi-Psi angles. 34

35 Molecular Surfaces 35

36 Electrostatic Potentials Useful for evaluating the effects of a potential mutation Analysis of binding site 36

37 SPDBV Home Page 37

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39 Persistence of Vision (POV) RAY Visualization Ray tracing occurs from the camera to the scene Specify Camera location Light sources Objects Surface textures Atmospheric media (fog, haze, or fire) 39

40 POV RAY 40

41 PovRay Molecules... Armand Tepper s Energy minimized Yeast Cu-metallothionein from an averaged NMR structure. 6 copper atoms are in the reddish metal texture and the sulfurs of the coordinating cysteines appear in yellow. This picture features the new smoother ribbon feature (quality 2) implemented in SPDBV3.6b2. The surface is at detail level

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43 POV Ray scene generators Swiss PDB Viewer can save file as POV scene PDB to POV converters available MolPov (windows) der_pov2.htm PPOVIT (PERL) ppovit/ 43

44 PyMOL Set of structure tools built on top of Python Supports all Standard Features Extensible, Scriptable Native Ray Tracer Freely Available: 44

45 PyMOL Set of structure tools built on top of Python Supports all Standard Features Extensible, Scriptable Native Ray Tracer Freely Available: 45

46 PyMOL External GUI Command line interface Standard menu bar Some Handy Buttons 46

47 PyMOL External GUI Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 47

48 PyMOL Actions Menu (A) Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 48

49 PyMOL Show Menu (S) Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 49

50 PyMOL Hide Menu (S) Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 50

51 PyMOL Labels Menu (L) Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 51

52 PyMOL Color Menu (C) Named Groups Panel VIEWING WINDOW Mouse Bindings Command Line Movie Controls 52

53 Hen egg-white lysozyme and tri-n-acetylchitotriose 53

54 Conclusions Several of the more powerful structure tools with visualization and structure manipulation features are freely available Rasmol, Cn3D, Swiss PDB Viewer, PyMOL Mark up your structures to convey important and useful information Ray Trace output scenes for best rendering and artistic flash 54